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Effects of combined administration of FK 506 and the purine biosynthesis inhibitors mizoribine or mycophenolic acid on lymphocyte DNA synthesis and T cell activation molecule expression in human mixed lymphocyte cultures

Thomson, AW and Woo, J and Yao, GZ and Todo, S and Starzl, TE and Zeevi, A (1993) Effects of combined administration of FK 506 and the purine biosynthesis inhibitors mizoribine or mycophenolic acid on lymphocyte DNA synthesis and T cell activation molecule expression in human mixed lymphocyte cultures. Transplant Immunology, 1 (2). 146 - 150. ISSN 0966-3274

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Abstract

Our objective was to obtain new information on the in vitro antilymphocytic action of the cytokine synthesis inhibitor FK 506 and the purine biosynthesis inhibitors mycophenolic acid (MPA; the active moiety of RS61443) and mizoribine (MZB) when used alone or in combination. When added at the initiation of six-day human mixed lymphocyte cultures (MLC), FK 506, MPA or MZB exhibited dose-dependent inhibition of T-lymphocyte DNA synthesis. FK 506, however, was 100-fold more potent than MPA, and 10000-fold more potent than MZB. Combination of FK 506 with either MPA or MZB, each at suboptional concentrations, produced no more than additive inhibitory effects on 3H thymidine incorporation. Two-colour flow cytometric analysis of lymphocytes revealed that none of the drugs affected cell surface activation molecule expression (CD25 = IL-2R 55 kD α-chain, HLA-DR or CD71 = transferrin receptor [TR]) on allostimulated CD4+ or CD8+ cells harvested at three days of culture. By day six, however, all three agents, at levels which markedly inhibited proliferation, suppressed the expression of activation markers on both CD4+ and CD8+ cells. Also at day six, inhibition of activation molecule expression on CD4+ cells was achieved with the combination of FK 506 and either MPA or MZB at concentrations which, on their own, were ineffective. These data provide new, additional information on the in vitro antilymphocytic action of FK 506, MPA and MZB when used alone and in combination. © 1993.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Thomson, AW
Woo, J
Yao, GZ
Todo, S
Starzl, TEtes11@pitt.eduTES11
Zeevi, A
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1993
Date Type: Publication
Journal or Publication Title: Transplant Immunology
Volume: 1
Number: 2
Page Range: 146 - 150
DOI or Unique Handle: 10.1016/0966-3274(93)90009-w
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0966-3274
Other ID: uls-drl:31735062113471, Starzl CV No. 1556
Date Deposited: 08 Apr 2010 17:26
Last Modified: 04 Feb 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/4942

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